The overall objective of this proposal is to understand the mechanisms which control selective immunological reactivity and non-reactivity to "modified self" antigens in the T cell-mediated lympholytic system. Recently, we have reported a new method for generating hapten-specific synreactive cytotoxic T cells in vivo without eliminating cyclophosphamide sensitive suppressor T cells. It essentially consists of injecting H-2 compatible, minor histoincompatible auxiliary cells simultaneously with hapten-modified syngeneic stimulator cells. The cytolytic T cells which proved to be genetically restricted were recoverable from the lymph nodes draining the injection sites. In view of these findings it has become imperative to establish the cellular basis for the significant enhancement of the synreactive killer T cell response when M1s disparate auxiliary cells are included and also to reassess the relative role of helper T cells and suppressor T cells in the development of cytotoxic T cells. In vivo as well as in vitro experiments will be conducted using mouse spleen cells pre-selected on the basis of Ly phenotypes to study the role of different T cell subsets and their products in generating the synreactive cytotoxic T cell response. We anticipate that information obtained from experiments outlined in this proposal will permit identification of functional control points in the development of killer T cells operative in the syngeneic lympholytic system and that such knowledge may become useful to the areas of immunological tolerance, auto immunity, and graft as well as tumor rejection.